ALA-based photodynamic priming in murine skin increases blood flow and oxygenation.

Abstract

Significance: Topical photodynamic therapy (PDT) with protoporphyrin IX (PpIX) converted from 5-aminolevulinic acid (ALA) is a well-established noninvasive method of treating skin conditions and lesions. During PDT, there can be response dynamics within the tissue that are affected by the light delivery, seen with fractionated delivery and in subcurative priming delivery. Fractionated light doses can considerably increase efficacy of 5-ALA PDT response.

Aim: We aim to examine the changes in physiological blood flow, tissue oxygenation, and PpIX concentration during and after light delivery in topical ALA-PDT in nude mouse skin.

Approach: We compared three schemes of light delivery for topical ALA-PDT in nude mice, including (1) full light delivery without fractionation, (2) two equal fractions (50% and 50%) of light separated by 2 h, and (3) a 5% light dose fractionation by 2 h prior to the main 95% light dose. Tissue oxygen imaging was assessed with the hypoxia signal from delayed fluorescence of PpIX itself within the tissue, as well as by confirmation with Oxyphor phosphorescence lifetime quenching imaging.

Results: The results of blood flow imaging and hypoxia imaging from PpIX and oxygen imaging with Oxyphor each showed evidence of increased capillary flow and tissue oxygenation after the initial 5% light dose, increased at the side of irradiation. This increased capillary flow and tissue oxygenation are presumably from vasodilation and local capillary flow increase. PpIX replenishment occurs during the intervening dark period after the initial light delivery.

Conclusion: These observations suggest that increasing oxygen and capillary flow combined with increased PpIX production together yield increased PDT efficiency, amplified by this initial light dose from a photodynamic optical priming event occurring 2 h prior to full PDT light delivery.